Stem cells refer to cells having not only self-replicating ability but also the ability to differentiate into at least two types of cells, and can be divided into totipotent stem cells, pluripotent stem cells, and multipotent stem cells. Totipotent stem cells are cells having totipotent properties capable of developing into one perfect individual, and these properties are possessed by cells up to the 8-cell stage after the fertilization of an oocyte and a sperm. When these cells are isolated and transplanted into the uterus, they can develop into one perfect individual. Pluripotent stem cells, which are cells capable of developing into various cells and tissues derived from the ectodermal, mesodermal and endodermal layers, are derived from an inner cell mass located inside of blastocysts generated 4-5 days after fertilization. These cells are called “embryonic stem cells” and can differentiate into various other tissue cells but not form new living organisms. Multipotent stem cells, which are stem cells capable of differentiating into only cells specific to tissues and organs containing these cells, are involved not only in the growth and development of various tissues and organs in the fetal, neonatal and adult periods but also in the maintenance of homeostasis of adult tissue and the function of inducing regeneration upon tissue damage. Tissue-specific multipotent cells are collectively called “adult stem cells”.
Adult stem cells are obtained by taking cells from various human organs and developing the cells into stem cells and are characterized in that they differentiate into only specific tissues. However, recently, experiments for differentiating adult stem cells into various tissues, including liver cells, were dramatically successful, which comes into spotlight. In particular, efforts have been made in the field of regenerative medicine for regenerating biological tissues and organs and recovering their functions that were lost due to illness or accident and the like by using cells. Methods which are frequently used in this field of regenerative medicine comprise the steps of: collecting stem cells, blood-derived mononuclear cells or marrow-derived mononuclear cells from a patient; inducing the proliferation and/or differentiation of the cells by tube culture; and introducing the selected undifferentiated (stem cells and/or progenitor cells) and/or differentiated cells into the patient's body by transplantation. Accordingly, existing classical methods for treating diseases by medication or surgery are expected to be replaced with cell/tissue replacement therapy which replaces a damage cell, tissue or organ with healthy one, and thus the utility of stem cells will further increase.
Thus, the various functions of stem cells are currently being studied. Particularly, since cell therapy technologies using mesenchymal stem cells started to receive attention, technologies for improving mesenchymal stem cells isolated from a human body so as to be suitable for therapeutic purposes have been developed (WO 2006/019357, Korean Patent No. 0795708, and Korean Patent No. 0818214).
Meanwhile, the function of the body's organs or the ability of cells to self-renew decreases with age. Similar to this phenomenon, the function and morphology of stem cells can change when the stem cells are repeatedly cultured in vitro or are stimulated by external factors. In other words, the moment the culture of cells in vitro is started, the cells start to lose their function and enter a senescence state, even though the loss of the function is almost not perceivable. Because such characteristics of cells, it is preferable to use early-stage cells for gene therapy, and it is also preferable to use stem cells that do not significantly change their characteristics, such as proliferation ability, differentiation ability, phenotype, morphology and activity, even when the stem cells are cultured for a long period of time. Thus, studies on such cells are in progress (BMC Cell Biology 2006, 7:14, Aging Research Reviews 5, 2006, 91116).
Accordingly, the present inventors have made extensive efforts to find medium components which can enhance the self-renewal ability of stem cells without changing the characteristics (such as morphology or activity) of the stem cells even when the stem cells are repeatedly cultured. As a result, the present inventors have found that, when stem cells are cultured in a medium composition containing apelin, the ability of the stem cells to self-renew can be enhanced, thereby completing the present invention.